The objective of this proposal is to determine the ability of inactivated whole cell (IWC) vaccine and inactivated whole virus (IWV) vaccine to protect against FIV infection and to determine their mechanisms of action. The IWC vaccine will consist of inactivated FIV-infected allogeneic lymphoid cells. The IWV vaccine will consist of inactivated cell-free pelleted FIV. The proposed objective will be achieved through the following specific aims: (1) Evaluate the efficacies of the IWC and IWV vaccines by testing their relative abilities to protect cats against FIV infection and disease upon live FIV challenge from both homologous (same FIV strain as vaccine) and heterologous (different strain) sources. The immunogenicity of the vaccines will be determined by monitoring the development of cellular and humoral responses to several FIV proteins in vaccinated cats. Cats will be challenged with low and high doses of FIV and monitored for signs of FIV infection and clinical symptoms; and (2) Determine the mechanisms of action of the IWC and IWV vaccines. This will be done by evaluating the types of humoral and cellular immunities elicited by the vaccines before and after the live virus challenge. Cats will be challenged at various intervals after immunization; and humoral and cellular immune responses will be monitored. In this way, the development of immune responses can be monitored, thereby allowing determination of the minimal response required to protect against FIV. Passive immunization with antibodies from vaccinated cats will be performed on unexposed cats prior to their challenge with FIV. This will determine the significance of the humoral immunity in the prophylaxis of FIV infection and disease. Cats will be immunized with lymphoid cells from vaccinated siblings (adoptive transfer) to determine the role of cellular immunity in FIV protection. The early phase of our studies has demonstrated that both the IWC and IWV vaccines are effective in protecting cats against FIV infection. Significant levels of FIV neutralizing antibodies have been detected in IWC-vaccinated cats. Thus, this study should help define the requirements for effective vaccines against FIV and perhaps against other lentiviruses.